Epigenetic silencing of the tumor suppressor genes SPI1, PRDX2, KLF4, DLEC1, and DAPK1 in childhood and adolescent lymphomas

The aim of the study was to investigate the expression and methylation status of seven distinctive genes with tumor suppressing properties in childhood and adolescent lymphomas. A total of 96 patients with Hodgkin Lymphoma (HL, n = 41), Non-Hodgkin Lymphoma (NHL, n = 15), and reactive lymphoid hyperplasia (RLH, n = 40, as controls) are included in the research. The expression status of CDKN2A, SPI1, PRDX2, DLEC1, FOXO1, KLF4 and DAPK1 genes were measured with QPCR method after the RNA isolation from paraffin blocks of tumor tissue and cDNA conversion. DNA isolation was performed from samples with low gene expression followed by methylation PCR study specific to promoter regions of these genes. We found that SPI1, PRDX2, DLEC1, KLF4, and DAPK1 genes are significantly less expressed in patient than the control group (p = 0.0001). However, expression of CDKNA2 and FOXO1 genes in the patient and control groups were not statistically different. The methylation ratios of all genes excluding the CDKN2A and FOXO1 were significantly higher in the HL and NHL groups than the controls (p = 0.0001). We showed that SPI1, PRDX2, DLEC1, KLF4 and DAPK1 genes are epigenetically silenced via hypermethylation in the tumor tissues of children with HL and NHL. As CDKN2A gene was not expressed in both patient and control groups, we conclude that it is not specific to malignancy. As FOXO1 gene was similarly expressed in both groups, its relationship with malignancy could not be established. The epigenetically silenced genes may be candidates for biomarkers or therapeutic targets in childhood and adolescent lymphomas.     

The impact of mode of delivery on the sexual function of primiparous women: a prospective study

Aim

The purpose of this study was to evaluate the impact of mode of delivery on the sexual function of women using the Female Sexual Function Index (FSFI).

Methods

This was a prospective study of 452 nulliparous women, comparing their sexual function before and after birth. A Turkish version of the FSFI questionnaire was administered within the first 8 weeks of pregnancy, at 3 and 6 months postpartum in a face-to-face manner and subsequently at the 12th month and 24th month over the telephone.

Results

Age, BMI, education level, house income, duration of marriage, birthweight, and feeding at each time point were similar between group 1 [vaginal birth and mediolateral episiotomy (MLE)] and group 2 [caesarean section (CS)]. In the postpartum period, there were 265 and 138 participants at 3rd month, 216 and 121 participants at 6th month, 189 and 111 participants at 12th month, and 133 and 85 participants at 24th month in group 1 and 2, respectively. The FSFI total scores decreased at 3 and 6 months postpartum in both groups (27.3 to 23.1 in group 1 and 27.5 to 25 in group 2; p?<?0.05 for both). Desire, arousal, lubrication, satisfaction and pain scores were significantly decreased at 3 months postpartum in group (1) In group 1, desire, arousal and pain scores remained decreased at the 6th month compared to initial scores. Group 2 had significantly lower desire, lubrication, satisfaction and pain scores at 3 months postpartum compared to their initial scores. Decline in desire and lubrication domains persisted at the 6th month for group (2) None of the FSFI domain scores differed after 6th months when compared to pre-delivery scores in both groups. Compared with the caesarean group, the vaginal birth with MLE group had lower satisfaction and higher pain levels at 3 months postpartum (p?<?0.0001, for both). None of the FSFI domains differed at the 6th, 12th or the 24th month between the groups.

Conclusion

Our study revealed that caesarean section is not superior to vaginal birth in terms of preservation of normal sexual function, regardless of short-term postpartum effects. Women should be informed that, irrespective of their type of delivery, sexual function 6 months after childbirth is similar to that in pre-pregnancy.

     

Diffusion-weighted MR imaging of thyroid nodules

Introduction  The purpose of our study was to determine the diagnostic role of diffusion-weighted imaging (DWI) in the differentiating of malignant and benign thyroid nodules by using fine needle aspiration biopsy cytology criteria as a reference standard. The apparent diffusion coefficient (ADC) values of the normal-looking thyroid parenchyma were also evaluated both in normal patients and in patients with nodules. Methods  Between March 2007 and February 2008, 76 consecutive patients with ultrasound-diagnosed thyroid nodules and 20 healthy subjects underwent diffusion-weighted MR imaging by using single-shot spin echo, echo planar imaging. A total of 93 nodules were included in the study using the following b factors 100, 200, and 300 mm²/s. ADC values of thyroid nodules and normal area in all subjects were calculated and compared using suitable statistical analysis. Results  Mean ADC values for malignant and benign nodules were and for b-100 factor, and for b-200, and and , for b-300, respectively. Mean ADC values of malignant nodules were lower than benign nodules. There were significant differences in ADC values between benign and malignant nodules. ADC values among normal-appearing thyroid parenchyma of patients and normal-appearing thyroid parenchyma of healthy subjects were insignificant at all b factors. Conclusion  Benign nodules have higher ADC values than malignant ones. DWI may be helpful in differentiating malign and benign thyroid nodules.     

Hepatoprotective Effect of Infliximab,an Anti-TNF-α Agent,on Carbon Tetrachloride-Induced Hepatic Fibrosis

To assess the effect of infliximab, an anti-tumor necrosis factor (TNF)-α agent, on the carbon tetrachloride (CCl₄)-induced hepatic fibrosis in rats. Rats were randomized into three groups (n = 9). The control group received only intraperitoneal (i.p.) olive oil. Hepatic fibrosis was induced by repeated i.p. injections of 1.5 ml/kg CCl₄ (1:3 mixture with olive oil) for 5 weeks in the remaining two groups which were also injected subcutaneous saline or 2 mg/kg infliximab. Infliximab reduced the levels of aspartate aminotransferase and alanine aminotransferase (p < 0.05 for both). The scores of hepatic necrosis, inflammation and fibrosis, and expression of α-smooth muscle actin were lower in the infliximab-treated group than the CCI₄-treated group (p < 0.01, p < 0.001, p < 0.01, p < 0.001, respectively). However, there was no significant difference in terms of liver tissue and plasma malondialdehyde, and serum TNF-α levels, while infliximab relatively reduced the level of transforming growth factor-β₁ (373.0 ± 153.1 vs. 280.8 ± 127.1 pg/ml). Treatment with infliximab attenuated the necro-inflammation and fibrogenesis in the CCI₄-induced hepatic fibrosis, and thus it might be effective as a therapeutic anti-fibrotic agent.     

Serum lipoprotein (a) levels and Behçet's disease: is there an association?

Background Behçet's disease (BD) is a multisystemic inflammatory disorder found in individuals with a particular genetic background. Hemostatic studies in BD support an imbalance towards a prothrombotic state at different levels. Lipoprotein (a) (Lp(a)) has atherogenic and thrombogenic properties. It is mostly under genetic regulation. We investigated the possible relationship between Lp(a) and BD. Methods Forty patients diagnosed with BD and 40 healthy controls were enrolled. The clinical characteristics of the patients were recorded. Serum total cholesterol, high-density lipoprotein (HDL), very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), apolipoprotein A1, apolipoprotein B, and Lp(a) levels of the two groups were assessed and compared statistically. Results All patients (100%) had oral aphthous ulcers. Thirty (75%) had genital ulceration, 37 (92.5%) had either erythema nodosum or papulopustular lesions, and 10 (25%) had eye involvement. Twelve (30%) had a positive pathergy test. Four (10%) had vascular involvement. The Lp(a) level of the patient population was 19.6 ± 18.8 mg/dL. This level was higher than that of the controls, but not statistically significant. The Lp(a) levels of the four patients with vascular complications were within normal limits. Conclusions Lp(a) is of interest, as it is a genetically determined parameter that was found to be high in BD patients in our study group. The levels were independent of thrombotic complications, perhaps suggesting a different role for this lipoprotein in the etiopathogenesis of BD. Further studies with a larger number of patients are essential to discover the exact role of Lp(a) in BD.     

Urological complications of congenital nephrogenic diabetes insipidus––long-term follow-up of one patient

A male with a severe form of congenital nephrogenic diabetes insipidus (diuresis 10 l per day) had megaureters, megavesica, large residuum and a history of three traumatic ruptures of the megavesica and a recurrent urinary tract infection (RUTI). Hemodialysis was introduced at 41 years of age. At age of 42, he underwent a bilateral retroperitoneoscopic nephrectomy to prevent further RUTI and 8 months later transplantation of a cadaver kidney. Intermittent catheterization is necessary due to residual urine in the urinary bladder.